Peptides containing the sequence Arg-Gly-Asp antagonize binding of fibrinogen to its platelet GPIIb/IIIa receptor, thereby inhibiting platelet aggregation. Incorporation of the sequence into cyclic pentapeptide disulfides has been reported to yield effective antagonists. The conformations in solution of two such antagonists, (2-mercaptobenzoy1)-Na-methylArgGly-Asp-2-mercaptoanilide cyclic disulfide (1) and Ac-Cys-Na-methylArg-Gly-A~p-Pen-NH~ cyclic disulfide (2), have been studied using a constrained distance geometry search procedure in conjunction with proton NMR data, and a structure of 1 has been determined from single-crystal X-ray diffraction data. NMR spectra of the cyclic diaryl disulfide 1 at 203 K in methanol show two slowly exchanging conformations. The Arg-Gly-Asp region of the major form is characterized, inter alia, by an extended Gly residue flanked by an Na-methylArg residue in a conformation roughly consistent with the i + 2 position of a &turn and an Asp residue in a C7 like conformation. In the minor component, the Asp residue is near the aR conformation. The bamer to exchange between the two forms is estimated at 11 kcal/mol. NMR data and analysis of the constrained distance geometry search results suggest that, at room temperature in dimethyl sulfoxide-sulfolane, the dominant conformation of the Arg-Gly-Asp regions of both 1 and 2 is like that in the major component of 1 at 203 K. (2-Mercaptobenzoy1)-Na-methylArg-Gly-Asp-2-mercaptoanilide cyclic disulfide (1) was crystallized from aqueous ethanol as a solvated nitrate salt in a cell of dimensions a = 27.919 (16) A, b = 7.552 (3) A, c = 16.3131 (10) A, and j 3 = 108.79 (5)' with four formula units in space group C2. The structure was solved by direct methods and refined to R = 0.057 for 2869 observations (I 2 340). The crystal structure of 1 and the most probable conformation of its minor form in solution agree closely.

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Dilute hydrogen bromide in trifluoroacetic acid containing pentamethylbenzene and thioanisole was used in the cleavage and deprotection of peptides on MBHA‐resin. Particular attention was paid to potential applicability of the method to kilogram scale synthesis of thymosin α1. In the HPLC purification of the peptides, acetonitrile was replaced by relatively nontoxic isopropanol. The change should be economically and environmentally very attractive.